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NIH		NCRR Software Tools for Receptor-Based Drug Design			Budget Code:
The goal of this activity is to develop computational methodologies for use in the design of drugs. This endeavor includes the establishment of high performance computer-based environments that: accurately and efficiently estimate electrostatic forces in molecular and atomic interactions; effectively employ core computer technologies to calculate drug-protein binding energies from quantum mechanics, statistical mechanics and simulation techniques; and eventually attain dramatic improvements in performance of molecular dynamics programs to permit theoretical and experimental studies to be executed in similar time frames.							Budget ($ M) FY 95 Act 2.50 FY 96 Pres 2.20 FY 96 Est 2.20 FY 97 Rqst 2.20 Program Component Areas   FY 96 FY 97 HECC 2.20 2.20 LSN     HCS     HuCS     ETHR     Agency Ties DARPA   NSF Partner DOE   NASA   NIH   NSA   NIST   NOAA   EPA   ED   AHCPR   VA
Milestone Changes
FY 1995 Actual Milestones			FY 1996 Estimated Milestones	FY 1997 Agency Requested Milestones
Continued refinement of high performance computer-based environments to include access to state-of-the-art massively parallel computers, new algorithms and software specifically tailored for use on these systems, and updated interfaces with high speed networks. Access to resource center facilities available to scientists nationally to conduct drug design research. Tested the ability to predict binding constants of known molecule-drug combinations, for example, a known HIV protease-drug inhibitor. Use of new methods for calculating solvation energies to determine the solubilities of candidate pharmaceuticals prior to chemical synthesis.			Use of high performance resources accessible through high speed networks will enable structure-based design of drugs to become a reality in the pharmaceutical industry. Design of new molecule-drug combinations using capability to predict protein-drug binding energies. Work on calculation of solvation energies should uncover overestimates in certain binding energies, e.g., hydrogen binding. New potential functions must be developed for biomolecular modeling to become quantitative. Support new investigator-initiated research project grants.	Continue use of high performance computer resources accessible through high speed networks to support structure- based drug design. Improve methods to efficiently and accurately predict protein-drug binding energies. Enhance simulations of complex protein-drug interactions on/in cellular membranes. Support new investigator-initiated research project grants.